Selective retina therapy (SRT) is a laser treatment modality for those retinal diseases that are thought to result from a dysfunctional retinal pigment epithelium (RPE). Examples of such diseases include diabetic macular edema, central serous retinopathy and drusen (commonly associated with early AMD).
The laser used in SRT applies a train of green microsecond pulses to the retina. Most of the laser light (≈50%) is initially absorbed by the RPE cells that are loaded with melanosomes; about 7% of the incident light is absorbed in the photoreceptors.
According to the principle of selective photothermolysis, one can selectively destroy tissue and avoid harming adjacent structures by choosing a wavelength that is preferentially absorbed by the target tissue and illuminating the tissue using that wavelength with a pulse that is shorter than the thermal relaxation time of the absorber.
The RPE is an ideal model to test the accuracy of selective targeting because it strongly absorbs visible light (due to its high content of melanosomes) and is surrounded by sensitive but less absorbing neural tissue. The thermal relaxation time of a single melanosome (TRTmel) is only about 0.4 μs, while the thermal relaxation time of an RPE cell (TRTRPE) is over an order of magnitude longer, or about 5 μs. Because the pulse duration in SRT is on the order of TRTmel and shorter than TRTRPE, heat diffusion away from the RPE cells into the neural retina is minimized. As a result, photoreceptors can be preserved.
It has been shown that, following selective destruction of RPE cells, surviving bystander cells cover the lesion within 7-14 days. The therapeutic benefit is thought to arise from the recovery of RPE cells, where new RPE cells are capable of removing existing drusen or edema.
The lasers that create the necessary pulse energy and pulse structure in SRT are large and complicated devices that may be difficult to implement in a clinical setting. Therefore, practical scanning SRT systems use a CW laser, rather than a pulsed laser. In such systems, a scanner rapidly moves the spot of a CW laser over the retina to produce microsecond-long exposure at each irradiated RPE cell. The spot diameter of the scanning device is about the size of one RPE cell (≈15 μm). By adjusting the scanning speed and scan pattern, one can control the extent of damage. For example, by adjusting the settings to minimize heat diffusion into adjacent tissues, one can selectively damage individual RPE cells. By changing the settings to facilitate heat diffusion into adjacent layers, one can instead carry out conventional thermal coagulation of neural retina.
In both, scanning and pulsed SRT, lesions are generally not visible in slit lamp examination. Therefore, the clinical endpoint associated with conventional retinal laser photocoagulation, the whitening of the retina due to thermal coagulation, is not available. Instead, one typically waits an hour after treatment to verify treatment success. The lack of any real-time feedback mechanism carries the risk of unsuccessful treatment, which would require re-treatment. However, the lack of real-time feedback also carries the risk of over-treatment by accidentally exceeding the RPE cell damage threshold of an individual patient. This over-treatment can result in collateral retinal damage and laser scotoma. Consequently, an alternative feedback mechanism that evaluates treatment outcome during the irradiation is desirable for eventual clinical application.
RPE cell damage in SRT was originally thought to be accomplished by thermal necrosis. Over the past years, it has been shown that rapid heating of melanosomes by nano- or microsecond pulses can lead to formation of microscopic bubbles. Vaporization associated with cavitation is initiated when the surface temperature of the melanosome reaches about 150° C. The cavitation extends to a size of a few micrometers around the absorbing melanosome and typically collapses within 1 μs.